Alveolar rhabdomyosarcoma: novel surrogate markers associated with oncogenic translocation

Tarakanova A.V.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Sharlai A.S.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

ORCID: 0000-0001-5354-7067

Konovalov D.M.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology;
Russian Medical Academy of Continuous Professional Education

ORCID: 0000-0001-7732-8184

Alveolar rhabdomyosarcoma: novel surrogate markers associated with oncogenic translocation

Authors:

Tarakanova A.V., Sharlai A.S., Konovalov D.M.

More about the authors

Journal: Russian Journal of Archive of Pathology. 2023;85(1): 10‑15

DOI: 10.17116/patol20238501110

Downloaded: 152

Download PDF (RU)

Contact the author

Table of contents

To cite this article:

Tarakanova AV, Sharlai AS, Konovalov DM. Alveolar rhabdomyosarcoma: novel surrogate markers associated with oncogenic translocation. Russian Journal of Archive of Pathology. 2023;85(1):10‑15. (In Russ.)
https://doi.org/10.17116/patol20238501110

Подписка 2025-2 (Russian Journal of Archive of Pathology)

Close metadata

BACKGROUND

Anomalies of the FOXO1 gene in alveolar rhabdomyosarcoma are associated with a worse clinical prognosis, which determines the high value of studying the status of this gene when choosing a therapy strategy. The «gold standard» for determining FOXO1 gene rearrangements is currently the fluorescent in situ hybridization (FISH) technique.

OBJECTIVE

Study of the relationship between canonical FOXO1 translocation and immunohistochemical expression of new surrogate markers in alveolar rhabdomyosarcoma to determine their predictive value.

MATERIAL AND METHODS

139 cases of rhabdomyosarcoma were retrospectively studied. The study used tissue matrix technology (TMA). On sections obtained from TMA blocks, the FISH technique was implemented using the locus-specific probe MetaSystems XL FOXO1 Break Apart (Metasystems, Germany). Immunohistochemical studies were performed on similar sections from TMA blocks with OLIG2 (Cell Marque Antibodies, clone 211F1.1) and MUC4 (Cell Marque Antibodies, clone 8G7) antibodies.

RESULTS

The final expression analysis and statistical processing using a 2x2 contingency table and Fisher’s exact test passed 111 cases (76 without FOXO1 rearrangement and 35 with rearrangement). The specificity of OLIG2 and MUC4 expression for FOXO1-rearranged alveolar rhabdomyosarcoma was 85.53% and 80.26%, respectively (p<0.01).

CONCLUSION

The present study confirms the high predictive value of the expression of surrogate markers OLIG2 and MUC4 in determining the genetic status of alveolar rhabdomyosarcoma, which makes it possible to predict with high specificity the detection of the FOXO1 gene rearrangement.

Keywords:

rhabdomyosarcoma

alveolar

FOXO1

PAX3

PAX7

OLIG2

MUC4

MyoD1

surrogate markers

Authors:

Tarakanova A.V.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

Sharlai A.S.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology

ORCID: 0000-0001-5354-7067

Konovalov D.M.

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology;
Russian Medical Academy of Continuous Professional Education

ORCID: 0000-0001-7732-8184

Received:

14.09.2022

Accepted:

26.10.2022

List of references:

Leiner J, Le Loarer F. The current landscape of rhabdomyosarcomas: an update. Virchows Arch. 2020;476(1):97-108. https://doi.org/10.1007/s00428-019-02676-9
Agaram NP. Evolving classification of rhabdomyosarcoma. Histopathology. 2022;80(1):98-108. https://doi.org/10.1111/his.14449
Botiralieva GK, Sharlai AS, Roshchin VJu, Sidorov IV, Konovalov DM. Rabdomiosarkomy: strukturnoe raspredelenie i analiz immunogistokhimicheskogo profilya. Arkhiv patologii. 2020;82(5): 33-41. (In Russ.). https://doi.org/10.17116/patol20208205133
WHO Classification of Tumours Editorial Board. WHO Classification of Tumours. Soft tissue and bone tumours. 5th ed. Vol. 3. World Health Organization; 2020.
Putnam AR, Thomson KS, Wallentine JC. Diagnostic pathology: pediatric neoplasms. 2nd ed. Elsevier; 2018.
Sharlai AS, Botiralieva GK, Drui AE, Roshchin VJu, Konovalov DM. Rasprostranennost’ anomalii gena FOXO1 v gruppe kruglokletochnykh rabdomiosarkom s al’veolyarnoi morfologiei. Voprosy gematologii/onkologii i immunopatologii v pediatrii. 2020;19(4): 82-87. (In Russ.). https://doi.org/10.24287/1726-1708-2020-19-4-82-87
Rudzinski ER. Histology and fusion status in rhabdomyosarcoma. Am Soc Clin Oncol Educ Book. 2013;425-428. https://doi.org/10.14694/EdBook_AM.2013.33.425
Giannikopoulos P, Parham DM. Rhabdomyosarcoma: how advanced molecular methods are shaping the diagnostic and therapeutic paradigm. Pediatr Dev Pathol. 2021;24(5):395-404. https://doi.org/10.1177/10935266211013621
Sun W, Chatterjee B, Wang Y, Stevenson HS, Edelman DC, Meltzer PS, Barr FG. Distinct methylation profiles characterize fusion-positive and fusion-negative rhabdomyosarcoma. Mod Pathol. 2015;28(9):1214-1224. https://doi.org/10.1038/modpathol.2015.82
Kashi VP, Hatley ME, Galindo RL. Probing for a deeper understanding of rhabdomyosarcoma: insights from complementary model systems. Nat Rev Cancer. 2015;15(7):426-439. https://doi.org/10.1038/nrc3961
Williamson D, Missiaglia E, de Reyniès A, Pierron G, Thuille B, Palenzuela G, Thway K, Orbach D, Laé M, Fréneaux P, et al. Fusion gene-negative alveolar rhabdomyosarcoma is clinically and molecularly indistinguishable from embryonal rhabdomyosarcoma. J Clin Oncol. 2010;28(13):2151-2158. https://doi.org/10.1200/JCO.2009.26.3814
Aye JM, Chi YY, Tian J, Rudzinski ER, Binitie OT, Dasgupta R, Wolden SL, Hawkins DS, Gupta AA. Do children and adolescents with completely resected alveolar rhabdomyosarcoma require adjuvant radiation? A report from the Children’s Oncology Group. Pediatr Blood Cancer. 2020;67(5):e28243. https://doi.org/10.1002/pbc.28243
Cooperative Weichteilsarkom Study Group CWS der GPOH in cooperation with the European paediatric Soft Tissue Sarcoma Study Group EpSSG, CWS-guidance for risk adapted treatment of soft tissue sarcoma and soft tissue tumours in children, adolescents, and young adults. Version 1.5. from 01.07.2009. 2009;252.
Skapek SX, Anderson J, Barr FG, Bridge JA, Gastier-Foster JM, Parham DM, Rudzinski ER, Triche T, Hawkins DS. PAX-FOXO1 fusion status drives unfavorable outcome for children with rhabdomyosarcoma: a children’s oncology group report. Pediatr Blood Cancer. 2013;60(9):1411-1417. https://doi.org/10.1002/pbc.24532
Kaleta M, Wakulińska A, Karkucińska-Więckowska A, Dembowska-Bagińska B, Grajkowska W, Pronicki M, Łastowska M. OLIG2 is a novel immunohistochemical marker associated with the presence of PAX3/7-FOXO1 translocation in rhabdomyosarcomas. Diagn Pathol. 2019;14(1):103. https://doi.org/10.1186/s13000-019-0883-4
Raghavan SS, Mooney KL, Folpe AL, Charville GW. OLIG2 is a marker of the fusion protein-driven neurodevelopmental transcriptional signature in alveolar rhabdomyosarcoma. Hum Pathol. 2019;91:77-85. https://doi.org/10.1016/j.humpath.2019.07.003
Forgo E, Hornick JL, Charville GW. MUC4 is expressed in alveolar rhabdomyosarcoma. Histopathology. 2021;78(6):905-908. https://doi.org/10.1111/his.14321

Close metadata